Acute Antero-Inferior Wall Ischaemia with Acute Ischaemic Stroke Caused by Oral Ingestion of Cannabis in a Young Male.

Cannabis is a frequently used illicit recreational drug that is known to be associated with a variety of psychopharmacological effects. Negative somatic effects such as myocardial infarction and stroke have been reported, though, less frequently. Most of the literature available has focused on the complications due to smoked forms of cannabis (ganja and charas). Here we report a case of acute myocardial ischaemia with acute ischaemic stroke developing after oral ingestion of 'Bhang', a preparation of cannabis.

Effect of quercetin on lipopolysaccharide induced-sickness behavior and oxidative stress in rats.

OBJECTIVES: Gram-negative infections and control infusion of recombinant cytokines in human have been shown to induce sickness behavior characterized by fever, prolong sleep, decreased food and water intake, reduced mobility, depression, and anxiety. Therefore, the present study was undertaken to investigate the effect of bioflavonoid quercetin in lipopolysaccharide (LPS)-induced sickness behavior. MATERIALS AND METHODS: Wistar albino rats were divided into six groups (n=6). Three groups received vehicle and two doses of quercetin (2 and 25 mg/kg, i.p.) respectively for 2 weeks before being challenged with LPS (1 mg/kg, i.p). One group received vehicle for 2 weeks and was challenged with saline on day 15. The per se effect of quercetin (2 and 25 mg/kg, i.p.) was also seen after 2 weeks of dosing. LPS-induced sickness behavior in rats was quantified by measuring time in social exploration, anxiety, food and water consumption, and weight loss. Levels of cytokines (TNF-α, IL-1ß, and IL-6) and oxidative stress in rat brain were also analyzed. RESULTS: Quercetin (2 and 25 mg/kg) administration significantly (P<0.05) attenuated LPS-induced sickness behavior by modulating cytokines production as well inhibiting LPS-induced oxidative stress. CONCLUSIONS: Adequate intake of dietary flavonoids (like quercetin) may help promote recovery from sickness behavior.

A young female patient of neuromyelitis optica presenting with hypocalcemic tetany.

Neuromyelitis optica, a variant of multiple sclerosis, presenting with hypocalcemic tetany is an unusual presentation. We report here a case of 25 years old female who was a case of neuromyelitis optica and had hypocalcemic tetany as the initial presentation among others. The case is interesting in that the hypocalcemic tetany was not coincidental. The patient had low vitamin D status and probably, this was correlated etiologically to neuromyelitis optica. Vitamin D has immunomodulatory effect and low vitamin D status has been implicated in the etiology of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory bowel disease.

Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model.

Chronic fatigue syndrome, infection and oxidative stress are interrelated in epidemiological case studies. However, data demonstrating scientific validation of epidemiological claims regarding effectiveness of nutritional supplements for chronic fatigue syndrome are lacking. This study is designed to evaluate the effect of natural polyphenol, curcumin, in a mouse model of immunologically induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigens were used as immunogens. The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 min daily for 19 days and the immobility time was taken as the marker of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time and hyperalgesia on day 19, as well as marked increase in serum tumor necrosis factor-alpha (TNF-alpha) levels. Concurrent treatment with curcumin resulted in significantly decreased immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as TNF-alpha levels. These findings strongly suggest that during immunological activation, there is significant increase in oxidative stress and curcumin can be a valuable option in the treatment of chronic fatigue syndrome.

Effect of curcumin on inflammation and oxidative stress in cisplatin-induced experimental nephrotoxicity.

Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Recent evidence suggests that inflammation and oxidative stress may contribute to the pathogenesis of cisplatin-induced acute renal failure. Curcumin is claimed to be a potent anti-inflammatory and antioxidant agent. The present study was performed to explore the effect of curcumin against cisplatin-induced experimental nephrotoxicity. Curcumin in the dosages of 15, 30, and 60 mg kg(-1) was administered 2 days before and 3 days after cisplatin administration. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, urea clearance, and serum nitrite levels. Renal oxidative stress was assessed by determining renal malondialdehyde levels, reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase. Systemic inflammation was assessed by tumor necrosis factor-alpha (TNF-alpha) levels. A single dose of cisplatin resulted in marked inflammation (486% rise in TNF-alpha level) and oxidative stress and significantly deranged renal functions as well as renal morphology. The serum TNF-alpha level was markedly reduced in curcumin-treated rats. Curcumin treatment significantly and dose-dependently restored renal function, reduced lipid peroxidation, and enhanced the levels of reduced glutathione and activities of superoxide dismutase and catalase. The present study demonstrates that curcumin has a protective effect on cisplatin-induced experimental nephrotoxicity, and this effect is attributed to its direct anti-inflammatory and strong antioxidant profile. Hence, curcumin has a strong potential to be used as a therapeutic adjuvant in cisplatin nephrotoxicity.

6-Gingerol prevents cisplatin-induced acute renal failure in rats.

BACKGROUND: Nephrotoxicity is a major complication and a dose limiting factor for cisplatin therapy. Recent evidence suggests that enhanced oxidative stress caused by oxygen-centered free radicals may contribute to the pathogenesis of cisplatin-induced acute renal failure. 6-Gingerol is claimed to be a potent antioxidant. The present study was performed to explore the renoprotective potential of 6-gingerol on cisplatin-induced oxidative stress and renal dysfunction. METHODS: 6-Gingerol in dosages of 12.5, 25, 50 mg/kg was administered 2 days before and 3 days after cisplatin administration. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, urea clearance and serum nitrite levels. Renal oxidative stress was assessed by determining renal malondialdehyde levels, reduced glutathione levels and enzymatic activities of superoxide dismutase and catalase. RESULTS: A single dose of cisplatin resulted in marked renal oxidative and nitrosative stress and significantly deranged renal functions. 6-Gingerol treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation and enhanced the levels of reduced glutathione and activities of superoxide dismutase and catalase. CONCLUSIONS: The present study demonstrates the renoprotective potential of 6-gingerol against cisplatin-induced oxidative stress and renal dysfunction in rats. Hence, 6-gingerol has a potential to be used as therapeutic adjuvant in cisplatin nephrotoxicity.

Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity.

Hesperidin (HDN) is a flavanone glycoside abundantly found in citrus fruits. HDN has been reported to possess significant activities against allergy, haemorrhoids, hormonal disorders and ulcers. Other reported activities include anti-inflammatory, analgesic, antibacterial, antifungal, antiviral, antioxidant and free radical scavenger activity. A potentially important effect of endotoxin is the increased production of reactive oxygen intermediates as O(2)(-), peroxides and nitric oxide. The study reported here show a beneficial effect of HDN in amelioration of endotoxin-induced hepatic dysfunction and oxidative stress in the liver of rats. Hepatotoxicity was induced by administering lipopolysaccharide (LPS), in a single dose of 1mg/kg intraperitoneally to the rats. A marked hepatic dysfunction evident by rise in serum levels of liver enzymes (ALT, AST, ALP) and total bilirubin (p<0.05) was observed. Serum and tissue nitrite levels were also increased. LPS challenge further increased thiobarbituric acid reactive substances (TBARS) levels, whereas glutathione (GSH) content and superoxide dismutase (SOD) activity were decreased in the liver homogenates of the rats showing a marked oxidative stress. HDN administration successfully and dose dependently attenuated these effects of LPS. In conclusion, these findings suggest that HDN attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of NO and oxygen free radicals.

Are the increases in local tumour necrosis factor and lipid peroxidation observed in pre-starved mice infected with Salmonella typhimurium markers of increased liver damage?

Pathogenic microorganisms are known to sense and process signals within their hosts, including those resulting from starvation. Therefore, an attempt was made to evaluate the extent and the possible underlying mechanism of Salmonella typhimurium-induced hepatic damage using pre-starved laboratory mice. The following parameters were analysed, comparing control, fed infected, starved, and starved infected mice: the bacterial load in the liver, fluctuations in liver-derived enzymes alanine-aminotransferase and aspartate-aminotransferase, histopathological changes, lipid peroxidation as well as estimation of reduced glutathione, superoxide dismutase and catalase, along with the TNF content in livers. The number of bacterial cells recovered from starved infected livers at 3 days post-S. typhimurium inoculation was comparable to the number recovered from fed infected livers at 5 days post-Salmonella inoculation, indicating an early increase in the development of the bacteria in starved mice. A marked elevation in liver-derived enzymes in mouse serum and significant histopathological changes are markers of liver damage of higher amplitude in starved infected mice. Analysis of the liver indicated a significant increase in lipid peroxidation in starved infected mice compared to their control counterparts, a process coupled with increased TNF level. Although the reduced glutathione levels showed a marked increase in the starved infected mice, there was a significant decrease in superoxide dismutase and catalase activities in this group.

Renoprotective effect of Spirulina fusiformis on cisplatin-induced oxidative stress and renal dysfunction in rats.

Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide array of both pediatric and adult malignancies. Dose-dependent and cumulative nephrotoxicity is the major toxicity of this compound, sometimes requiring a reduction in dose or discontinuation of treatment. Recent evidences have implicated oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Spirulina fusiformis, blue-green algae, is claimed to be a potential antioxidant. The present study was designed to explore the renoprotective potential of Spirulina fusiformis against cisplatin-induced oxidative stress and renal dysfunction. Spirulina fusiformis (500,1000,1500 mg/kg(-1) p.o.) was administered 2 days before and until 3 days after cisplatin challenge (5 mg/kg(-1) i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance, and serum nitrite levels. Renal oxidative stress was determined by renal TBARS levels, reduced glutathione levels, and by enzymatic activity of superoxide dismutase and catalase. A single dose of cisplatin produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic Spirulina fusiformis treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the present study clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of Spirulina fusiformis in cisplatin-induced nephrotoxicity.

Effect of Spirulina, a blue green algae, on gentamicin-induced oxidative stress and renal dysfunction in rats.

Gentamicin (GM), an aminoglycoside, is widely employed in clinical practice for the treatment of serious Gram-negative infections. The clinical utility of GM is limited by the frequent incidence of acute renal failure. Experimental evidences suggest that oxidative and nitrosative stress play an important role in GM nephrotoxicity. Spirulina fusiformis is a blue green algae with potent free radical scavenging properties. The present study was designed to investigate renoprotective potential of S. fusiformis, against GM-induced oxidative stress and renal dysfunction. Spirulina fusiformis (500, 1000, 1500 mg/kg, p.o.) was administered 2 days before and 8 days concurrently with GM (100 mg/kg, i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen and creatinine clearance and serum nitrite levels. Renal oxidative stress was determined by renal malondialdehyde levels, reduced glutathione levels and by enzymatic activity of superoxide dismutase (SOD) and catalase. Chronic GM administration resulted in marked renal oxidative and nitrosative stress and significantly deranged renal functions. Treatment with S. fusiformis significantly and dose-dependently restored renal functions, reduced lipid peroxidation and enhanced reduced glutathione levels, SOD and catalase activities. The results of present study clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of S. fusiformis in GM-induced nephrotoxicity.

Green tea (Camellia sinensis) extract ameliorates endotoxin induced sickness behavior and liver damage in rats.

Immune activation, either by cytokines or endotoxin, elicits a constellation of nonspecific symptoms such as weakness, malaise, listlessness, fatigue, adipsia, anorexia, depression and anxiety collectively termed as sickness behavior. Further, endotoxin administration in animals has been implicated in the pathogenesis of many types of liver disease. Green tea, a common household drink, is rich in antioxidant polyphenols demonstrating inhibitory effects on cytokine production. The present study was designed to investigate the effect of chronic treatment of green tea extract (GTE) on lipopolysaccharide (LPS)-induced sickness behavior and liver damage in rats. The hypothesis was tested through the analysis of LPS-induced behavioral changes in rats, in plus maze and open field paradigms. Other parameters such as feeding and water consumption, weight loss and organ weight index were also estimated. Liver function tests were conducted to investigate the effect of GTE supplementation on LPS-induced hepatic dysfunction. The results of the study demonstrated that GTE significantly attenuated LPS-induced sickness behavior as well as hepatic damage either by its antioxidant activity or by inhibiting LPS induced cytokine production in rats.

Green tea [Camellia sinensis (L.) O. Kuntze] extract reverses the despair behaviour in reserpinised and diabetic mice.

Green tea (C. sinensis) extract (GTE) dose dependently produced reversal of despair in normal, reserpinised and diabetic mice, thereby demonstrating an antidepressant effect. Although the exact mechanism is yet to be explored, the possible inhibition of catechol-o-methyl transferase and monoamine oxidase enzymes may be responsible for antidepressant activity of GTE.

Curcumin, a diferuloylmethane, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rat kidneys.

BACKGROUND: In India, Curcumin (CMN) is popularly known as "Haldi", and has been well studied due to its economic importance. Traditional Indian medicine claims the use of its powder against biliary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorder, rheumatism and sinusitis. This study was designed to examine the possible beneficial effect of CMN in preventing the acute renal failure and related oxidative stress caused by chronic administration of cyclosporine (CsA) in rats. CMN was administered concurrently with CsA (20 mg/kg/day s.c) for 21 days. Oxidative stress in kidney tissue homogenates was estimated using thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) content, superoxide dismutase (SOD), and Catalase (CAT). Nitrite levels were estimated in serum and tissue homogenates. RESULTS: CsA administration for 21 days produced elevated levels of TBARS and marked depletion of renal endogenous antioxidant enzymes and deteriorated the renal function as assessed by increased serum creatinine, Blood Urea Nitrogen (BUN) and decreased creatinine and urea clearance as compared to vehicle treated rats. CMN markedly reduced elevated levels of TBARS, significantly attenuated renal dysfunction increased the levels of antioxidant enzymes in CsA treated rats and normalized the altered renal morphology. CONCLUSION: In conclusion our study showed that CMN through its antioxidant activity effectively salvaged CsA nephrotoxicity.

Resveratrol, a polyphenolic phytoalexin protects against cyclosporine-induced nephrotoxicity through nitric oxide dependent mechanism.

Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its use is frequently accompanied by severe renal toxicity. The causes for the nephrotoxicity of CsA have not been fully elucidated. Intrarenal vasoconstriction induced by several different mediators, both in humans and experimental animals have been proposed. The present study was designed to investigate the possible protective effect of resveratrol on CsA-induced nephrotoxicity and to explore the possible mechanism involved in resveratrol's effect. Eight groups of rats were employed in this study, group 1 served as control, group 2 rats were treated with olive oil (vehicle for CsA), group 3 rats were treated with CsA (20 mg/kg, s.c. for 21 days), groups 4, 5 and 6 received CsA along with resveratrol (2, 5 and 10 mg/kg, p.o. 24 h before and 21 days concurrently), respectively, group 7 rats were treated with NOS inhibitor, L-NAME (10 mg/kg) along with resveratrol and CsA and group 8 rats received L-NAME along with CsA. CsA administration for 21 days resulted in a marked renal oxidative stress, significantly deranged the renal functions, reduced the tissue and urine nitrite levels and markedly altered the renal morphology. Treatment with resveratrol (5 and 10 mg/kg) significantly improved the renal dysfunction; tissue and urine total nitric oxide levels, renal oxidative stress and prevented the alterations in renal morphology. Concurrent administration of L-NAME blocked the protective effect of resveratrol indicating that resveratrol exerts its protective effect by releasing nitric oxide. These results clearly demonstrate the pivotal role of nitric oxide in etiology of CsA nephrotoxicity and indicate the renoprotective potential of resveratrol in CsA nephrotoxicity.

Green tea extract and catechin ameliorate chronic fatigue-induced oxidative stress in mice.

Chronic fatigue syndrome (CFS) is an illness characterized by persistent and relapsing fatigue, often accompanied by numerous symptoms involving various body systems. The etiology of CFS remains unclear, but a number of studies have shown that oxidative stress may be involved in its pathogenesis. The present study was designed to investigate the protective effect of green tea extract (GTE) and catechin in the mouse model of CFS. Animals were subjected to a forced swimming test session of 6 minutes every day for 7 days; a significant increase in immobility time on successive days represented the CFS in mice. Biochemical analysis revealed that the chronic swim test significantly increased lipid peroxidation levels and decreased glutathione levels in mouse whole-brain homogenate. Treatment with GTE (25 or 50 mg/kg, i.p.) and catechin (50 or 100 mg/kg, i.p.) for 7 days reversed the increase in immobility time. Protection was correlated with the lowered levels of lipid peroxidation and restoration of reduced glutathione levels in the brains of fatigued mice. These findings strongly suggest the pivotal role of oxidative stress in the pathophysiology of CFS and that GTE and catechin could be used as potential agents in the management of CFS and warrant the inclusion of GTE and catechin in the treatment regimen of CFS patients.

Reversal of LPS-induced central and peripheral hyperalgesia by green tea extract.

Tea has recently attracted a great deal of attention for its beneficial health effects. Green tea polyphenols inhibit the production of arachidonic acid metabolites and leukotrienes resulting in decreased inflammatory responses. In the present study, the effect of green tea extract (GTE) on lipopolysaccharide (LPS)-induced thermal and behavioural hyperalgesia in mice and the possible involvement of the cyclooxygenase pathway in this paradigm was evaluated. GTE (25 mg/kg, i.p.), nimesulide (2 mg/kg, i.p.) and rofecoxib (2 mg/kg, i.p.) significantly attenuated LPS-induced thermal and behavioural hyperalgesia but per se did not modify any of the behavioural effects. Concurrent administration of a subeffective dose of GTE (10 mg/kg, i.p.) and rofecoxib (2 mg/kg, i.p.) or nimesulide (2 mg/kg, i.p.) significantly potentiated the antinociceptive effect of GTE in both LPS-induced thermal and behavioural hyperalgesia with nimesulide showing a more pronounced enhancing effect. Thus it can be concluded that GTE attenuates LPS-induced central and peripheral hyperalgesia by selective inhibition of cyclooxygenase-2 enzyme.

Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney.

BACKGROUND: CCl4 is a well-established hepatotoxin inducing liver injury by producing free radicals. Exposure to CCl4 also induces acute and chronic renal injuries. The present study was designed to establish the protective effect of hesperidin (HDN), a citrus bioflavonoid, on CCl4-induced oxidative stress and resultant dysfunction of rat liver and kidney. METHODS: Animals were pretreated with HDN (100 and 200 mg/kg orally) for one week and then challenged with CCl4 (2 ml/kg/s.c.) in olive oil. Rats were sacrificed by carotid bleeding under ether anesthesia. Liver enzymes, urea and creatinine were estimated in serum. Oxidative stress in liver and kidney tissue was estimated using Thiobarbituric acid reactive substances (TBARS), glutathione (GSH) content, superoxide dismutase(SOD), and Catalase (CAT) RESULTS: CCl4 caused a marked rise in serum levels of ALT and AST (P < 0.05). TBARS levels were significantly increased whereas GSH, SOD and CAT levels decreased in the liver and kidney homogenates of CCl4 treated rats. HDN (200 mg/kg) successfully attenuated these effects of CCl4 CONCLUSION: In conclusion, our study demonstrated a protective effect of HDN in CCl4 induced oxidative stress in rat liver and kidney. This protective effect of HDN can be correlated to its direct antioxidant effect.

Amelioration of cyclosporine nephrotoxicity by irbesartan, A selective AT1 receptor antagonist.

Cyclosporine A (CsA), a fungal undecapeptide, is the most common immunosuppressive drug used in organ transplantation and autoimmune diseases. However, nephrotoxicity is the major adverse effect of CsA use. The molecular mechanisms of CsA nephrotoxicity are not well characterized, but more recent studies suggest an involvement of angiotensin II (ANG II) and reactive oxygen species in the development of cyclosporine nephrotoxicity. Induction of heat shock proteins (HSPs) is one of the best-described cellular responses to heat stress, hypoxia, and exposure to oxidants. HSPs have beneficial roles in protein processing and protection against cell injury. There is emerging evidence that ANG II induces oxidative stress in vitro and in vivo. This study was thus designed to investigate the role of Angiotensin II type I (AT1) receptor antagonist, irbesartan, on CsA-induced nephrotoxicity. Five groups of rats were employed in this study: group 1 served as control, group 2 rats were treated with CsA (20 mg kg(-1), subcutaneously for 21 days), and groups 3, 4, and 5 received CsA along with irbesartan (10, 25, and 50 mg kg(-1), perorally 24 hr before and 21 days concurrently), respectively. Renal function was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, and urea clearance. The renal oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels, and enzymatic activity of catalase, glutathione reductase, and superoxide dismutase. Renal morphological alterations were assessed by histopathological examination. CsA administration for 21 days resulted in a marked renal oxidative stress and significantly deranged the renal functions as well as renal morphology. All these factors were significantly improved by irbesartan (50 mg kg(-1)) treatment. HSP72, HSP47, and HSP25 were clearly induced and expressed in CsA-treated animals. The induction and expression of HSP25 was markedly protected by treatment with irbesartan, whereas the induction and expression of HSP47 and HSP72 remained unaltered with the irbesartan treatment. These results clearly demonstrate the pivotal role of ANG II-induced oxidative stress and therapeutic potential of AT, receptor antagonist in ameliorating CsA-induced nephrotoxicity.

Reversal of LPS-induced immobility in mice by green tea polyphenols: possible COX-2 mechanism.

An endotoxin (lipopolysaccharide, LPS) is known to activate the hypothalamo-pituitary adrenocortical axis, as well as norepinephrine and indolamine metabolism. Systemically administered LPS produces depression in the forced swimming-induced despair behaviour model in mice. The present study was designed to investigate the effect of green tea extract (GTE) on LPS-induced despair behaviour and to explore the mechanism involved in modulation of LPS-induced immobility by GTE. GTE (10-100 mg/kg) pretreatment reversed LPS-induced immobility in a dose-dependent manner. Rofecoxib (2 mg/kg) and nimesulide (2 mg/kg), COX-2 inhibitors, also reversed the LPS-induced immobility, which was significantly potentiated by concomitant administration of GTE. On the other hand, GTE did not show any potentiating effect on immobility with naproxen (10 mg/kg), which is a nonselective COX blocker. Interestingly the antioxidant, carvedilol (2 mg/kg) did not produce any effect on immobility either in normal or in LPS treated mice. The results of the study implicate the role of COX-2 inhibition by GTE in the reversal of LPS-induced immobility.

Attenuation of cyclosporine-induced renal dysfunction by catechin: possible antioxidant mechanism.

One of great use of immunosuppressant, Cyclosporine-A (CsA) is in the solid organ transplantation; however the extensive use of this is cautionable due to its toxic effect in renal tissue, characterized by the tubular atrophy, interstitial fibrosis, and progressive renal impairment. However, there are many mediators are associated with pathogenesis of nephrotoxicity of CsA, the exact mechanism is still in debate. Recent studies indicate that Reactive Oxygen Species (ROS) induced oxidative stress and lipid peroxidations are the important mechanisms implicated in the pathophysiology of nephrotoxicity with CsA. In the present study we examined effect of dietary flavonoid catechin on oxidative damage in cyclosporine-A induced nephrotoxicity. Chronic administration of CsA (20 mg/kg/day) subcutaneously for 21 days significantly decreased the body weight as compared with vehicle treated rats. CsA (20 mg/kg/day) administration for 21 days significantly decreased the renal function by increase in the serum creatinine, blood urea nitrogen, and decrease in the creatinine and urea clearance as compared with vehicle treated rats. Catechin (100 mg/kg/day) for 21 days along with CsA significantly reversed the changed renal parameters, however lower dose of catechin (50 mg/kg/day) restored only increased serum creatinine levels as compared with CsA alone treated group. Biochemical analysis revealed that chronic administration of CsA (20 mg/kg/day) for 21 days significantly induced lipid peroxidation and decreased the glutathione levels in the kidney homogenate of rats. It is also observed that chronic CsA administered rats showed decrease in antioxidant defense enzyme superoxide dismutase and increase in the catalase activity as compared with vehicle treated rats. Co-administration of catechin (100 mg/kg/day) orally along with CsA for 21 days significantly reduced the lipid peroxidation and restored the decreased glutathione levels as compared with CsA alone group, but lower dose of catechin (50 mg/kg/day) restored only decreased glutathione levels induced by CsA. Co-administration of only higher dose of catechin (100 mg/kg/day) along with CsA significantly increased the superoxide dismutase (SOD) levels as compared with CsA alone treated group. It is also observed that catechin (100 mg/kg/day) along with CsA further increased the catalase levels as compared with CsA alone treated group, but not with lower dose of catechin. Animals administered with catechin (100 mg/kg/day) alone for 21 days showed significant increase in the catalase levels as compared with vehicle treated group. The major findings of the present study suggest that oxidative stress might play a significant role in CsA-induced nephrotoxicity. In conclusion, dietary administration of flavonoid catechin could be a useful component for the prevention/treatment of CsA-induced nephrotoxicity.